The Notch gene family encodes single-pass, heterodimeric type I trans-membrane receptors. Notch signaling is activated by the DSL (Delta, Serrate, Lag-2) family of trans-membrane ligands between two neighboring cells and involves cell-cell communication. There are four Notch receptors and at least five mammalian ligands identified to date. Notch receptors are heterodimers, each consisting of an extracellular domain (ECN), a transmembrane domain, and an intracellular domain (ICN). ICN contains a RAM domain involved in CSL binding, ankyrin repeats (ANK), nuclear localization signals (NLS), and a PEST sequence. Transcriptional activation domain (TAD) differs among the four receptors. ECN contains multiple EGF-like repeats and LIN12/Notch repeats (LNR).
Notch signaling can begin with a ligand binding to the extracellular domain of Notch (ECN), which induces proteolytic cleavage and releases the active intracellular domain of Notch (ICN). ICN then translocates to the nucleus and binds to CSL, a DNA-binding transcriptional factor, and initiates the transcription of CSL-dependent Notch target genes.
G protein-coupled receptors (GPCRs) are known as seven-transmembrane domain receptors. GPCRs can mediate downstream signaling pathways via G proteins. Two of the signal transduction pathways involving GPCRs are cAMP and phosphatidylinositol signal pathways. There are five somatostatin receptor (SSTR) subtypes, three bombesin receptor subtypes, and three PACAP receptor subtypes, which belong to the GPCR superfamily
Somatostatin (SST), a somatotropin release-inhibiting factor (SRIF), also known as a growth hormone-inhibiting hormone (GHIH), is a peptide hormone with two active forms (SST-14 and SST-28) and can be secreted by endocrine cells. SST can act as an endogenous inhibitory regulator of a diverse array of cellular functions such as cell proliferation and hormone-release. SST can exert its functions by activating G protein-coupled SSTR or inhibiting release of growth factors.
Some embodiments of the invention include compositions comprising compositions or molecules that may take advantage of the above functions. Other embodiments, objects, and advantages of this invention will become readily apparent from the ensuing description.